MicroRNA-150 Suppresses Epithelial Mesenchymal Transition, Invasion and Metastasis in Prostate Cancer through the TRPM4-mediated β-catenin Signaling Pathway.

Research paper by Xi X Hong, Jian-Jun JJ Yu

Indexed on: 20 Dec '18Published on: 20 Dec '18Published in: American journal of physiology. Cell physiology


Prostate cancer (PCa) remains one of the leading causes of cancer-related deaths among males. The aim of the current study was to investigate the ability of microRNA-150 (miR-150) targeting transient receptor potential melastatin 4 (TRPM4) to mediate epithelial-mesenchymal transition (EMT), invasion and metastasis through the β-catenin signaling pathway in PCa. Microarray analysis was performed to identify PCa-related differentially expressed genes, after which both the mirDIP and TargetScan databases were employed in the prediction of the miRNAs regulating TRPM4. Immunohistochemistry and RT-qPCR were conducted to determine the expression pattern of miR-150 and TRPM4 in PCa. The relationship between miR-150 and TRPM4 expression was identified. By perturbing miR-150 and TRPM4 expression in PCa cells, cell proliferation, migration, invasion, cycle, apoptosis as well as EMT markers were determined accordingly. Finally, tumor growth and metastasis were evaluated among the nude mice. Higher TRPM4 expression and lower miR-150 expression, activation of the β-catenin signaling pathway as well as EMT stimulation were detected in the PCa tissues. Our results obtained confirmed TRPM4 as a target of miR-150. The upregulation of miR-150 resulted in the inactivation of the β-catenin signaling pathway. Furthermore, the upregulation of miR-150 or knockdown of TRPM4 was observed to suppress EMT, proliferation, migration and invasion in vitro in addition to restrained tumor growth and metastasis in vivo. The evidence provided by our study highlighted the involvement of miR-150 in the translational suppression of TRPM4 and the blockade of the β-catenin signaling pathway, resulting in the inhibition of PCa progression.

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